Anit-Virus Hydrophilic Polymeric Material

ABSTRACT

The invention provides a method for imparting antiviral properties to a hydrophilic polymeric material comprising preparing a hydrophilic polymeric slurry, dispersing an ionic copper powder mixture containing cuprous oxide and cupric oxide in said slurry and then extruding or molding said slurry to form a hydrophilic polymeric material, wherein water-insoluble particles that release both Cu ++  and Cu +  are directly and completely encapsulated within said hydrophilic polymeric material.

The present specification is a continuation in part of U.S. Ser. No.______ filed Jan. 6, 2004.

The present invention relates to a method for imparting antiviralproperties to a hydrophilic polymeric material, to hydrophilic polymericmaterials for inactivation of a virus and to devices incorporating thesame.

More particularly, the present invention relates to hydrophilicpolymeric materials incorporating a mixture of water-insoluble particlesthat release both Cu⁺⁺ and Cu⁺ wherein said particles are directly andcompletely encapsulated within said hydrophilic polymeric material.

In especially preferred embodiments, the present invention relates to amulti-layered hydrophilic polymeric material incorporating a mixture ofwater-insoluble particles that release both Cu⁺⁺ and Cu⁺.

In WO 01/74166 there is described and claimed an antimicrobial andantiviral polymeric material, having microscopic particles of ioniccopper encapsulated therein and protruding from surfaces thereof and therelevant teachings of said publication are incorporated herein byreference.

In said publication it is indicated that the polymeric material can beany synthetic polymer and examples which are mentioned are polyamides(nylon), polyester, acrylic, polypropylene, silastic rubber and latex.

As will be noted however, Example 1 of said patent related to thepreparation of a polyamide bi-component compound into which the copperpowder was added and the tests for antiviral, antifungal andantibacterial activity were carried out with said fibers.

In Example 4 of said patent, latex gloves were prepared however thesewere made from latex having microscopic particles of ionic copperprotruding from the surfaces thereof.

At the time of the writing of said specification it was believed thatall of the polymeric materials listed therein were effective asantimicrobial and antiviral only when the microscopic particles of ioniccopper were protruding from the surfaces of the polymeric material asseen e.g. in FIG. 1 of said publication.

According to the present invention it has now been surprisinglydiscovered that when working with a hydrophilic polymeric material it ispossible to produce a material and devices based thereon that possessantiviral properties even though the particles that release both Cu⁺⁺and Cu⁺ are directly and completely encapsulated within said hydrophilicpolymeric material.

In light of this surprising discovery which is neither taught norsuggested in said earlier specification, there is now provided accordingto the present invention a method for imparting antiviral properties toa hydrophilic polymeric material comprising preparing a hydrophilicpolymeric slurry, dispersing an ionic copper powder mixture containingcuprous oxide and cupric oxide in said slurry and then extruding ormolding said slurry to form a hydrophilic polymeric material, whereinwater-insoluble particles that release both Cu⁺⁺ and Cu⁺ are directlyand completely encapsulated within said hydrophilic polymeric material.

In preferred embodiments of the present invention said ionic copperpowder mixture is prepared by oxidation-reduction and preferably in thepreparation of said ionic copper powder said reduction is carried outusing formaldehyde as a reductant.

The invention also provides a hydrophilic polymeric material forinactivation of a virus comprising a mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric materialand are the primary active component therein.

In preferred embodiments of the present invention said particles are ofa size of between about 1 and 10 microns and preferably said particlesare present within said hydrophilic material in a concentration of about1 to 3 w/w %.

As indicated the present invention is specifically directed to impartingantiviral properties to a hydrophilic polymeric material and inpreferred embodiments of the present invention said hydrophilicpolymeric material is selected from the group consisting of latex,nitrile, acrylics, polyvinyl alcohol and silastic rubber.

According to the present invention there is also provided a thinhydrophilic polymeric coating comprising said mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric coatingmaterial and are the primary active component therein.

Such thin layer coatings can be applied on polymeric and othersubstrates and is especially useful for application to polymers, thepolymerization of which might be disrupted by the presence of cationicspecies of copper and or for the coating of latex polymeric articleswherein sensitivity to latex is problematic, such as in latex gloves andcondoms.

Based on the findings of the present invention it is now possible andthe present invention also provides a device for the inactivation of avirus brought in contact therewith, wherein said device is in the formof a nipple or nipple shield formed from a hydrophilic polymericmaterial comprising a mixture of water-insoluble particles that releaseboth Cu⁺⁺ and Cu⁺, which particles are directly and completelyencapsulated within said hydrophilic polymeric material.

The invention also provides a device for the inactivation of a virusbrought in contact therewith, wherein said device is in the form of abag formed from a hydrophilic polymeric material comprising a mixture ofwater-insoluble particles that release both Cu⁺⁺ and Cu⁺, whichparticles are directly and completely encapsulated within saidhydrophilic polymeric material and preferably said bag is a bloodstorage bag.

In further preferred embodiments of the present invention there isprovided a device for the inactivation of a virus brought in contacttherewith, wherein said device is in the form of a tube formed from ahydrophilic polymeric material comprising a mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric material.

Preferably said tube is a tube for transfer of body fluids such as bloodor milk.

In especially preferred embodiments of said device of the presentinvention said tube is provided with projections extending into thelumen thereof in order to cause mixing of the fluid flowing therethroughto assure contact of all of said fluid with surfaces of said polymericmaterial.

In a further aspect of the present invention there is provided a devicefor the inactivation of a virus brought in contact therewith, whereinsaid device is in the form of a condom formed from a hydrophilicpolymeric material comprising a mixture of water-insoluble particlesthat release both Cu⁺⁺ and Cu⁺, which particles are directly andcompletely encapsulated within said hydrophilic polymeric material andare the primary active component therein.

In yet another aspect of the present invention there is provided adevice for the inactivation of a virus brought in contact therewith,wherein said device is in the form of a diaphragm formed from ahydrophilic polymeric material comprising a mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric material.

The invention also provides a device for the inactivation of a virusbrought in contact therewith, wherein said device is in the form of aglove formed from a hydrophilic polymeric material comprising a mixtureof water-insoluble particles that release both Cu⁺⁺ and Cu⁺, whichparticles are directly and completely encapsulated within saidhydrophilic polymeric material.

The invention also provides a device for the inactivation of a virusbrought in contact therewith, wherein said device is in the form of aglove formed from a hydrophilic polymeric material and coated with athin layer of a further hydrophilic polymeric material, said furtherhydrophilic polymeric material comprising a mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric material.

In especially preferred embodiments of the present invention there isprovided a hydrophilic polymeric material for inactivation of a viruscomprising a mixture of water-insoluble particles that release both Cu⁺⁺and Cu⁺, which particles are directly and completely encapsulated withinsaid hydrophilic polymeric material and are the sole antiviral componenttherein.

In U.S. patent application Ser. No. 10/339,886 corresponding toPCT/IL03/00230, the relevant teachings of which are also incorporatedherein by reference there is described and claimed a device for theinactivation of a virus comprising a filtering material, said devicehaving ionic copper selected from the group consisting of Cu⁺ and Cu⁺⁺ions and combinations thereof incorporated therein.

In said specification there is described the plating of cellulose fibersusing a copper solution which results in the formation of copper oxideon the surface of said fibers wherein the process used yields both aCu(I) and a Cu(II) species as part of a copper oxide molecule. Saidfibers were then incorporated into a filter which was found to beeffective in the inactivation of HIV-1. Further tests with said filterrevealed that this combination was also effective in the inactivation ofWest Nile fever virus and the neutralization of adenovirus and thereforeit is believed that the antiviral hydrophilic polymeric materials of thepresent invention are also effective against such viruses since theywork on the same mechanism.

While the mechanism of the hydrophilic polymeric materials according tothe present invention is not fully understood, in light of the resultsobtained, it is believed that when the polymeric material is broughtinto contact with a fluid aqueous medium, said medium leaches thecationic species of copper from within said polymer and as described inPCT/IL03/00230 the antiviral activity takes advantage of the redoxreaction of the cationic species with water and allows a switch betweenCu (II) and Cu (I) when there is contact with water. Cu(I) is moreeffective than Cu(II) against HIV while Cu(II) is more stable thanCu(I). The Cu(II) compound will oxidize much more slowly than the Cu(I)compound and will increase the shelf life of the product.

As will be realized, in light of the now proven efficacy of cupric ionsin the inactivation of HIV, as more fully described in PCT/IL03/00230,the hydrophilic polymeric materials of the present invention can also beused for the solution of at least two major HIV problems which areplaguing the world.

The first of these problems is that in that in the third world countriesand especially in African countries entire populations are beingdecimated by HIV due to the transmission of HIV from infected mothers totheir newborn babies via nursing milk.

Due to the poverty prevalent in these countries milk substitutes are notavailable to newborn and nursing babies and infected mother's milk hasbeen found to be the major cause of transmission of HIV to children.

A further acute problem which also exists in the Western world is thefear of transfusion of HIV contaminated blood.

While blood banks now screen donated blood for HIV antibodies it isknown that the test for antibodies is only effective after theincubation period of 60-90 days and therefore there is always the dangerthat this screening process will not detect the blood of an individualwho only contracted HIV within 2 or 3 months of the donation.

Thus, as described hereinbefore, the present invention provides tubesfor the transfer of blood and bags for the storage of blood, thesurfaces of which are effective for inactivating viruses such as HIVvirus. Furthermore, the present invention provides nipples which can beused in breast shields of nursing mothers wherein milk passingtherethrough will undergo inactivation of any HIV virus containedtherein.

It will be realized that the device and method of the present inventionis not limited to the above mentioned preferred uses and that the devicecan also be used in a hospital or field hospital setting wherein bloodfrom a blood bank is not available and a direct transfusion is mandatedin that the preferred tubes of the present invention are provided withprojections extending into the lumen thereof in order to cause mixing ofthe fluid flowing therethrough to assure contact of all of said fluidwith surfaces of said polymeric material and thereby blood can betransferred through said tubes which would inactivate any virusescontained in said blood.

In further embodiments of the present invention the devices of thepresent invention can also be used to inactivate other viruses found inbody fluids including the inactivation of West Nile fever which has nowbeen discovered to exist in the blood of carriers of said disease who donot show symptoms thereof however whose blood could contaminate bloodbanks by transmission of said virus thereto.

As will be realized, once the water insoluble ionic copper compounds aremixed into a hydrophilic polymeric slurry, said slurry can be molded orextruded to form fibers, yarns, films, tubes, sheaths, bags, etc.wherein the water-insoluble particles that release both Cu⁺⁺ and Cu⁺ aredirectly and completely encapsulated within said hydrophilic polymericmaterial.

Unlike the fibers described, e.g. in WO 98/06508 and WO 98/06509, inwhich the fibers are coated on the outside, in the present product thepolymer has microscopic water insoluble particles of ionic copperdirectly and completely encapsulated therein. These fully encapsulatedparticles have been shown to be active, as demonstrated by the tests setforth hereinafter.

In WO 94/15463 there are described antimicrobial compositions comprisingan inorganic particle with a first coating providing antimicrobialproperties and a second coating providing a protective function whereinsaid first coating can be silver or copper or compounds of silver,copper and zinc and preferred are compounds containing silver and copper(II) oxide. Said patent, however, is based on the complicated andexpensive process involving the coating of the metallic compositionswith a secondary protective coating selected from silica, silicates,borosilicates, aluminosilicates, alumina, aluminum phosphate, ormixtures thereof and in fact all the claims are directed to compositionshaving successive coatings including silica, hydrous alumina and dioctylazelate.

In contradistinction, the present invention is directed to the use andpreparation of a hydrophilic polymeric material, wherein water-insolubleparticles that release both Cu⁺⁺ and Cu⁺ are directly and completelyencapsulated within said hydrophilic polymeric material which is neithertaught nor suggested by said publication and which has the advantagethat the Cu⁺⁺ and Cu⁺ releasing water insoluble particles have beenproven to be effective even in the inhibition of HIV-1 activity.

In EP 427858 there is described an antibacterial compositioncharacterized in that inorganic fine particles are coated with anantibacterial metal and/or antibacterial metal compound and said patentdoes not teach or suggest a hydrophilic polymeric material, whereinwater-insoluble particles that release both Cu⁺⁺ and Cu⁺ are directlyand completely encapsulated within said hydrophilic polymeric material.

In DE 4403016 there is described a bactericidal and fungicidalcomposition utilizing copper as opposed to ionic Cu⁺⁺ and Cu⁺ and saidpatent also does not teach or suggest a hydrophilic polymeric material,wherein water-insoluble particles that release both Cu⁺⁺ and Cu⁺ aredirectly and completely encapsulated within said hydrophilic polymericmaterial.

In JP-01 046465 there is described a condom releasing sterilizing ionsutilizing metals selected from copper, silver, mercury and their alloyswhich metals have a sterilizing and sperm killing effect, wherein themetal is preferably finely powdered copper. While copper salts such ascopper chloride, copper sulfate and copper nitrate are also mentioned asis known these are water soluble salts which will dissolve and breakdown the polymer in which they are introduced. Similarly, while cuprousoxide is specifically mentioned this is a Cu⁺ ionic form and thereforesaid patent does not teach or suggest the use of a hydrophilic polymericmaterial, wherein water-insoluble particles that release both Cu⁺⁺ andCu⁺ are directly and completely encapsulated within said hydrophilicpolymeric material, which has been proven to be effective even in theinhibition of HIV-1 activity.

In JP-01 246204 there is described an antimicrobial moulded article inwhich a mixture of a powdery copper compound and organic polysiloxaneare dispersed into a thermoplastic moulded article for the preparationof cloth, socks, etc. Said patent specifically states and teaches thatmetal ions cannot be introduced by themselves into a polymer moleculeand requires the inclusion of organopolysiloxane which is also intendedto provide a connecting path for the release of copper ions to the fibersurface. Thus, as will be realized said copper compound will beencapsulated and said patent does not teach or suggest the use of ahydrophilic polymeric material, wherein water-insoluble particles thatrelease both Cu⁺⁺ and Cu⁺ are directly and completely encapsulatedwithin said hydrophilic polymeric material.

In JP-03 113011 there is described a fiber having good antifungus andhygienic action preferably for producing underwear wherein saidsynthetic fiber contains copper or a copper compound in combination withgermanium or a compound thereof, however, said patent teaches andrequires the presence of a major portion of germanium and the coppercompounds disclose therein are preferably metallic copper, cuprousiodide which is a monovalent Cu⁺ compound and water soluble coppersalts. Thus, said patent does not teach or suggest the use of ahydrophilic polymeric material, wherein water-insoluble particles thatrelease both Cu⁺⁺ and Cu⁺ are directly and completely encapsulatedwithin said hydrophilic polymeric material.

In EP 116865 there is described and claimed a polymer article containingzeolite particles at least part of which retain at least one metal ionhaving a bacterial property and thus said patent does not teach orsuggest the use of Cu⁺⁺ and Cu⁺ releasing water insoluble particles, bythemselves and in the absence of a zeolite, which have been proven to beeffective even in the inhibition of HIV-1 activity.

In EP 253653 there is described and claimed a polymer containingamorphous aluminosilicate particles comprising an organic polymer andamorphous aluminosilicate solid particles or amorphous aluminosilicatesolid particles treated with a coating agent, at least some of saidamorphous aluminosilicate solid particles holding metal ions having abactericidal actions. Thus, said patent does not teach or suggest theuse of Cu⁺⁺ and Cu⁺ releasing water insoluble particles, by themselvesand in the absence of amorphous aluminosilicate particles, which havebeen proven to be effective even in the inhibition of HIV-1 activity.

As indicated hereinabove, the hydrophilic polymeric material of thepresent invention, having microscopic particles of ionic copper directlyand completely encapsulated therein, can also be utilized to manufacturedisposable gloves and condoms using a mold/form configuration.

In general, the chief raw material is concentrated and preserved naturalrubber latex. In addition such chemicals as acid, chlorine gases,alkalis, and corn/maize starch can be added, as is known in the art,however according to the present invention there is also added Cu⁺⁺ andCu⁺ in powder form.

Formers (or positive molds) are prepared through preparations that willkeep the liquid latex from sticking thereto. This is done through aseries of dips and treatments to the molds, as known per se in the art.The formers are then cleaned and dried and are dipped into a solution ofcoagulant chemicals. The coagulant forms a layer on the formers whichhelps to solidify latex when the formers are dipped into the latex tank.

The formers are dipped into the latex mixture, withdrawn therefrom andpassed through a curing oven. The gloves and/or condoms will bevulcanized as they pass through the different areas of the oven whichexpose the same to temperatures ranging from about 120 to 140° C. Thisprocess cross-links the latex rubber to impart the physical qualitiesrequired.

The difference between the normal process of manufacturing a disposableglove/condom and the process of the present invention is the addition ofwater insoluble particles that release Cu⁺⁺ and Cu⁺ in the rawmaterials.

In an especially preferred embodiment of the present invention themanufacturing process is varied in order to produce a multi-layeredhydrophilic polymeric material wherein at least one of the layers isprovided with water-insoluble particles that release both Cu⁺⁺ and Cu⁺which are directly and completely encapsulated within said hydrophilicpolymeric material and a second layer is substantially free of suchwater-insoluble particles.

As is known, the process for the production of products from naturallatex or nitrile begins with the naturally sapped or synthesized basecompound. The properties of the film created from the compound, such ashardness, flexibility, toughness, adhesion, color retention, andresistance to chemicals, depends on the composition of the plastic andthe additives that create different cross-linked polymers. Currently,most of these additives use a zinc cross linkage mechanism.

As is further known, copper will always displace zinc. However, thechemical qualities of copper do not allow the same linkage as zinc andare usually much weaker. Copper bonds in latex are very weak and willalways create quickly bio-degradable films thereby resulting in latexfilms having reduced structural integrity.

As described hereinbefore and as is known, a common technique used inthe creation of the film after the mixture of the latex with the properadditives in the form of e.g. a glove is the molding of the latex on ahand shaped figure. In order to control the dipping of the latex fromthe hand model, the model is treated with a calcium nitrate/calciumcarbonate coagulation of the raw materials which are then cured andcross-linked through heat and water removal. The coagulation is so quickand thorough that even after a dip of only a few seconds the mold isremoved from the liquid latex and no dripping occurs. This dip in thelatex is the creation of the actual glove. At that point, the glove goesthrough a series of ovens which cure the glove.

Normally, there is a finite limit to the thickness of the glove based onthe limited effect of the calcium compounds and viscosity of the latexsolution. It has now been surprisingly found according to the presentinvention that it is possible to extend the permeability of the calciumcompounds into more than one layer, provided the layers were relativelythin.

A highly diluted latex solution (about 70% water) was prepared to whicha copper powder was added. The mold was run through the calciumcompounds and then run through the diluted latex. It was observed thanan even thin layer was created on the mold. The mold was then placed inthe normal latex bath for the normal designated time. It wassurprisingly found that the mold had no problem in picking up andholding the same amount of latex as the molds which had not seen thelatex/copper solution.

What was yielded was a glove with the physical characteristics of aconventionally manufactured latex glove. The glove, after curing wasturned inside out, yielding a thin biologically active layer on theoutside and a conventional latex glove on the inside. It is impossibleto distinguish between the two layers of the glove. In order to makesure the layers were distinct a dye stuff was added to one layer and acolor differentiation between the two layers was obvious.

To further test the limits of the calcium compounds and their effect onthe latex, this same trial was done again but using 3 dips. The firstand third dips were copper/latex and the middle dip was a conventionallatex dip. A three layer glove was created that was slightly thickerthan a normal glove but again, impossible to differentiate from a normalglove.

In physical testing, the end products showed all the physicalcharacteristics of a conventional glove but showed effective biocidaland anti-viral qualities.

It will thus be realized that using this novel manufacturing process, itis possible to produce multi-layer hydrophilic polymeric materials suchas gloves, condoms, tubes, sheaths, bags, etc. wherein the structuralintegrity is provided by the layer which has not been treated toincorporate copper therein, while the anti-viral properties are providedby a thin outer layer, a thin inner layer, or both, which thin layershave water-insoluble particles that release both Cu⁺⁺ and Cu⁺ directlyand completely encapsulated within said thin hydrophilic polymericmaterial.

Thus in especially preferred embodiments of the present invention thereis now provided a device for the inactivation of a virus brought incontact therewith wherein said device is in the form of a nipple ornipple shield formed from a hydrophilic polymeric material, or in theform of a bag formed from a hydrophilic polymeric material or in theform of a tube formed from a hydrophilic polymeric material or in theform of a condom formed from a hydrophilic polymeric material or in theform of a diaphragm formed from a hydrophilic polymeric material or inthe form of a glove formed from a hydrophilic polymeric material andwherein in each of said devices said hydrophilic polymeric material is amulti-layered polymeric material comprising at least one layer providedwith water-insoluble particles that release both Cu⁺⁺ and Cu⁺ which aredirectly and completely encapsulated within said hydrophilic polymericlayer and a second hydrophilic polymeric layer which is substantiallyfree of such water-insoluble particles.

While the invention will now be described in connection with certainpreferred embodiments in the following examples and with reference tothe attached figures so that aspects thereof may be more fullyunderstood and appreciated, it is not intended to limit the invention tothese particular embodiments. On the contrary, it is intended to coverall alternatives, modifications and equivalents as may be includedwithin the scope of the invention as defined by the appended claims.Thus, the following examples which include preferred embodiments willserve to illustrate the practice of this invention, it being understoodthat the particulars shown are by way of example and for purposes ofillustrative discussion of preferred embodiments of the presentinvention only and are presented in the cause of providing what isbelieved to be the most useful and readily understood description offormulation procedures as well as of the principles and conceptualaspects of the invention.

In the drawings:

FIG. 1 is a graphical representation of the results of a comparativetest of HIV-1 inhibition; and

FIG. 2 is a graphical representation of the results of a comparativetest of Herpes Simplex Virus Type 1 inhibition.

EXAMPLE 1

-   a) An amount of copper oxide powder was produced through a reduction    oxidation process as known per se and as described in the    aforementioned prior art. In this production formaldehyde was used    as the reductant. The resulting powder was a dark brown color    indicating a mixture of cupric and cupous oxides.-   b) The powder was allowed to dry and was milled down to a particle    size of about 4 microns.-   c) An amount of bi-component latex was mixed and heated at a    temperature of about 150° C. so that it was in a liquid state ready    for molding.-   d) Three samples were made containing 1%, 2% and 3% by weight of the    powder within the latex. More specifically, in sample 1, 1 gram of    powder was added to 100 grams of the heated latex slurry, in sample    2, 2 grams of powder were added to 100 grams of the heated latex    slurry, and in sample 3, 3 grams of powder were added to 100 grams    of the heated latex slurry-   e) The resulting slurry was then molded to form a plurality of latex    bags.

With regard to the procedure described in Example 1, as will be realizedthe same system is applicable to any molding or extrusion process sincethe water insoluble copper containing compounds are added at the slurrystage. Thus, since the copper compounds are added at this stage ofproduction any product can be made through molding or extrusionincluding but not limited to gloves, tubes, sheaths, bags, nippleshields, condoms, diaphragms or any desired product.

It is to be noted that the only limitation is that the particle size ofthe copper compounds must be small enough so as not to disturb the flowof the slurry through extrusion machinery which is the reason for theuse of a particle size of about 4 microns in the above process. It isfurther to be noted that even with the addition of 3% by weight ofcopper compounds to the latex slurry, there was no discernibledifference in the viscosity of the slurry further confirming theversatility of the invention.

The finished product was placed under an electron microscope forobservation. No copper oxide particles could be identified by sight orthrough spectrographic readings on the surface of the molded productwhich was different than the observations made when the same process wascarried out using a polyester polymer.

In the case of a polyester fiber, it was noted that the particles of thecopper oxide compound, even when milled down to a 2 micron size, stillprotruded from the surface of the polymer.

EXAMPLE 2

A plurality of bags prepared according to Example 1 were sent to theRuth Ben-Ari Institute of Clinical Immunology and AIDS Center at theKaplan Medical Center in Israel for testing.

Method: Aliquots of medium containing HIV were placed in UV sterileCupron copper-containing latex bags or in UV sterile latex bags notcontaining copper. Virus stocks that were not exposed to any materialserved as positive controls for infectivity. As a negative control forviral activity, medium without any virus was placed in the Cupron coppercontaining bags. After 20 minutes of incubation at room temperature, 50μl drops from each of the bags were mixed with 40 μl fresh mediumcontaining 10% fetal calf serum (FCS), and each mixture was added totarget cells in 1 ml medium containing 10% FCS. The virus-cell mixtureswere then incubated in 24 well plates in a CO₂ humidified incubator at37° C. After four days of incubation the amount of virus present perwell was quantified.

Results: No viral infectivity was measured in the medium spiked withvirus and exposed to the Cupron copper containing bags or in thenon-spiked medium, while the viral infectivity of the medium containingvirus and exposed to a latex bag, which did not contain copper, weresimilar to that of the stock virus used.

Conclusion: The Cupron copper-containing latex bags deactivated thevirus.

Thus the results of Example 2 conclusively prove that a device accordingto the present invention is effective for inactivating viruses in fluidsbrought in contact therewith and thus e.g. blood storage bags accordingto the present invention can assure that blood stored therein will nottransmit a virus to a recipient of said blood.

EXAMPLE 3

Steps a, b and c of Example 1 are repeated however while in aconventional latex solution the normal water content is about 30-35%,the amount of water in the solution was doubled so that it was 70% waterand 30% latex.

To the 70% water/30% latex solution there was added 3% (calculated basedon the weight of the latex) a cuprous oxide compound comprising amixture of cuprous and cupric oxide powders wherein said powders wereformed of particles of up to 2 microns in diameter. The powder wasstirred into the latex solution and kept agitated to assure that itremained homogenous. The process was performed at room temperature.

A ceramic model of a hand was dipped into a calcium nitrate/calciumcarbonate solution sufficient to wet the model. The model was thendipped for up to 5 seconds in the diluted copper/latex solution. Themodel was spun on its axis to remove excess chemicals throughcentrifugal force. The model was then returned to the normal productionline where it was dipped in the conventional latex and allowed to gothrough normal production.

The glove after curing was then turned inside out and was found to havea thin biologically active layer on the outside having a thickness ofabout 80-100 microns and an inner layer having a thickness of about1000-1200 microns.

EXAMPLE 4

Gloves prepared according to Example 3 were tested for their anti-viralproperties wherein a double-layered natural latex glove as well as adouble-layered nitrile glove were prepared and tested.

EXAMPLE 4A Inhibition of HIV-1 Clade A

150 μl aliquots of HIV-1 Clade A stock virus were placed on top of aseries of double-layered Cupron latex gloves and on top of a series ofdouble-layered Cupron Nitrile gloves for 20 minutes at room temperature.As control, 150 μl of virus, which was not exposed to the gloves, wasincubated for 20 minutes at room temperature. The various virus aliquotswere then sequentially diluted (1:3 dilutions) in medium and thedilutions were added to MT-2 cells (T-cells susceptible to HIV-1infection), done in quadruplicates. The presence of syncytia formation,(indicative of virus infection) in the MT-2 cells was determined after 7days of culture at 37° C. in a moist incubator by an invertedmicroscope. This served as the basis to calculate the 50% Tissue CultureInfectious doses (TCID₅₀) as set forth in the Table in FIG. 1.

EXAMPLE 4B Inhibition of HSV-1

150 μl aliquots of Herpes Simplex Virus Type 1 (HSV-1) aliquots wereplaced on top of a series of double-layered Cupron Nitrile gloves for 20minutes at room temperature. As control, 150 μl of virus, which was notexposed to the glove, was incubated for 20 minutes at room temperature.Then, 5, 10, 20 or 40 μl of these viral aliquots were added to 293 cells(cells susceptible to HSV-1) grown in 1 ml culture medium (done induplicates). After 2 days of culture at 37° C. in a moist incubator thecytopathic effect of the virus (formation of plaques) was examined by aninverted microscope). As can be seen in FIG. 2 appended hereto, thegloves according to the present invention were effective at all of theviral concentrations to inhibit the same.

From the above Examples it is clear that the hydrophilic polymericmaterial and the devices according to the present inventionincorporating the same possess antiviral properties and their use forblood storage and transfer as well as for protective gloves, condoms,etc. provides a major advantage over the products presently available onthe market and can be a major boon for preventing viral transfer.

EXAMPLE 5

In order to further test the limits of the calcium compounds and theireffect on the latex, the procedure of Example 3 was repeated howeverusing 3 dips. The first and third dips were copper/latex and the middledip was a conventional latex dip. A three layer glove was created thatwas slightly thicker than a normal glove but again, impossible todifferentiate from a normal glove.

In physical testing, the end products showed all the physicalcharacteristics of a conventional glove but showed effective biocidaland anti-viral qualities.

The following Tables demonstrate that the structural integrity of aproduct according to the present invention is maintained when producinga double or triple layered glove as opposed to merely introducing thewater insoluble particles into a single layer product.

In Table 1 there is shown the testing of a normal latex glove whereinthe load peak is in the range of about 8.

In Table 2 there is shown the testing of a single layer latex glovehaving 1% copper oxide incorporated therein wherein the load peak isreduced to values between 6.5 and 7.7.

In Table 3 there is shown the testing of a triple layer latex gloveaccording to the present invention wherein while one glove showed a loadpeak of 7.4, the other three gloves tested showed load peaks of between8.6 and 10.1.

TABLE 1 TENSILE TEST REPORT TEST NO.: SAMPLE Test: RUBBER TENSILE PRO.DATE: Test Type: Tensile PRO. SHIFT: DAY Date: 31 Dec. 2003 COM. BA.NO.: Test Speed: 500.00 mm/min STYLE: SLAPT Sample Length:  070.0 mmR.P.M.: Sample Type: RECTANGULAR PLANT No.: Pre-Tension: OFF TESTED BY:DESAPRIYA Comments: CONTROL SAMPLE Stress @ Strain @ Stress @ Load @Test Width Thick. Peak Peak 500% Peak No. mm mm N/mm² % N/mm² N 1 3.00000.1350 20.385 777.42 5.9197 8.2560 2 3.0000 0.1350 20.842 745.24 6.51878.4410 Min. 3.0000 0.1350 20.385 745.24 5.9197 8.2560 Mean 3.0000 0.135020.614 761.33 6.2192 8.3485 Max. 3.0000 0.1350 20.842 777.42 6.51878.4410 S.D. 0.0000 0.0000 0.323 22.76 0.4236 0.1309

TABLE 2 TENSILE TEST REPORT TEST NO.: SAMPLE Test: RUBBER TENSILE PRO.DATE: Test Type: Tensile PRO. SHIFT: DAY Date: 31 Dec. 2003 COM. BA.NO.: Test Speed: 500.00 mm/min STYLE: LATEX Sample Length:  070.0 mmR.P.M.: Sample Type: RECTANGULAR PLANT No.: Pre-Tension: OFF TESTED BY:DESAPRIYA Comments: LB 1 Stress @ Strain @ Stress @ Load @ Test WidthThick. Peak Peak 500% Peak No. mm mm N/mm² % N/mm² N 1 3.0000 0.115020.038 799.49 5.1830 6.9130 2 3.0000 0.1250 20.251 823.34 4.6917 7.59403 3.0000 0.1250 20.749 807.36 4.9371 7.7810 4 3.0000 0.1200 18.303779.42 4.9384 6.5890 Min. 3.0000 0.1150 18.303 779.42 4.6917 6.5890 Mean3.0000 0.1213 19.835 802.40 4.9375 7.2193 Max. 3.0000 0.1250 20.749823.34 5.1830 1.7810 S.D. 0.0000 0.0048 1.064 18.25 0.2006 0.5618

TABLE 3 TENSILE TEST REPORT TEST NO.: LA1 3 DIP Test: RUBBER TENSILEPRO. DATE: 02 Jan. 2004 Test Type: Tensile PRO. SHIFT: DAY Date: 02 Jan.04 COM. BA. NO.: Test Speed: 500.00 mm/min STYLE: Sample Length:  070.0mm R.P.M.: Sample Type: RECTANGULAR PLANT No.: Pre-Tension: OFF TESTEDBY: RUVINI Comments: TUMBLING AT 70 C. Stress @ Strain @ Stress @ Load @Test Width Thick. Peak Peak 500% Peak No. mm mm N/mm² % N/mm² N 1 3.00000.1300 19.082 725.24 6.9383 7.442 2 3.0000 0.1900 17.153 753.06 5.298310.119 3 3.0000 0.1800 17.367 747.57 5.3093 9.378 4 3.0000 0.1800 15.967757.87 5.0437 8.622 Min. 3.0000 0.1300 15.967 725.24 5.0437 7.442 Mean3.0000 0.1700 17.542 745.94 5.6474 8.890 Max. 3.0000 0.1900 19.082757.87 6.9383 10.119 S.D. 0.0000 0.0271 1.282 14.42 0.8693 1.143

It will be evident to those skilled in the art that the invention is notlimited to the details of the foregoing illustrative examples and thatthe present invention may be embodied in other specific forms withoutdeparting from the essential attributes thereof, and it is thereforedesired that the present embodiments and examples be considered in allrespects as illustrative and not restrictive, reference being made tothe appended claims, rather than to the foregoing description, and allchanges which come within the meaning and range of equivalency of theclaims are therefore intended to be embraced therein.

1. A method for imparting antiviral properties to a hydrophilicpolymeric material comprising preparing a hydrophilic polymeric slurry,dispersing an ionic copper powder mixture containing cuprous oxide andcupric oxide in said slurry and then extruding or molding said slurry toform a hydrophilic polymeric material, wherein water-insoluble particlesthat release both Cu⁺⁺ and Cu⁺ are directly and completely encapsulatedwithin said hydrophilic polymeric material.
 2. A method according toclaim 1 wherein said ionic copper powder mixture is prepared byoxidation-reduction.
 3. A method according to claim 2 wherein saidreduction is carried out using formaldehyde as a reductant.
 4. Ahydrophilic polymeric material for inactivation of a virus comprising amixture of water-insoluble particles that release both Cu⁺⁺ and Cu⁺,which particles are directly and completely encapsulated within saidhydrophilic polymeric material and are the primary active componenttherein.
 5. A hydrophilic polymeric material for inactivation of a virusaccording to claim 4 wherein said particles are of a size of betweenabout 1 and 10 microns.
 6. A hydrophilic polymeric material forinactivation of a virus according to claim 4 wherein said particles arepresent within the hydrophilic material in a concentration of about 1 to3 w/w %.
 7. A hydrophilic polymeric material for inactivation of a virusaccording to claim 4, wherein said hydrophilic polymeric material isselected from the group consisting of latex, nitrile, acrylics,polyvinyl alcohol and silastic rubber.
 8. A hydrophilic polymericmaterial for inactivation of a virus according to claim 4, wherein saidpolymeric material is a multi-layered polymeric material comprising atleast one later provided with water-insoluble particles that releaseboth Cu⁺⁺ and Cu⁺ which are directly and completely encapsulated withinsaid hydrophilic polymeric layer and a second hydrophilic polymericlayer which is substantially free of such water-insoluble particles. 9.A hydrophilic polymeric material for inactivation of a virus accordingto claim 8, wherein said at least one layer and said second layer areformed of the same polymeric material.
 10. A device formed from ahydrophilic polymeric material comprising a mixture of water-insolubleparticles that release both Cu⁺⁺ and Cu⁺, which particles are directlyand completely encapsulated within said hydrophilic polymeric material.11. A device according to claim 10, wherein said hydrophilic polymericmaterial is a multi-layered polymeric material comprising at least onelayer provided with water-insoluble particles that release both Cu⁺⁺ andCu⁺ which are directly and completely encapsulated within saidhydrophilic polymeric layer and a second hydrophilic polymeric layerwhich is substantially free of such water-insoluble particles. 12-28.(canceled)